A 2-year-old male child born of third degree consanguineous marriage was brought to dermatology outpatient department with multiple dark colored flat lesions over body and one large dark colored flat lesion over right side of body since birth. Another prominent feature was proptosis of left eye since 1 month. Cutaneous examination revealed multiple café au lait macules (CALMs) over lower limbs and back and large CALM over right side of back, chest, and upper limb with proptosis of left eye. Histopathological examination of large patch findings was suggestive of CALM. Magnetic resonance imaging (MRI) brain plain and contrast findings were suggestive of plexiform neurofibroma. Based on clinical features and investigations a diagnosis of giant CALM in segmental distribution in a case of neurofibromatosis 1 (NF1) was made. It can be explained on basis of type II segmental manifestation in NF1.

A 2-year-old male child born of third degree consanguineous marriage was brought to dermatology outpatient department with multiple hyperpigmented macules with regular margins over back and thigh since birth [[Figure 1]a and b]. He also had a large hyperpigmented patch with regular border in segmental distribution (>30 cm) over right side of chest and back and right upper limb [[Figure 2]a and b]. There was proptosis of left eye [[Figure 3]a]. Axillary and inguinal freckling, cutaneous neurofibroma were absent. Palms, soles, hair, nails, oral cavity, dentition were normal. Kyphoscoliosis, tibial bowing were absent. No history of mental retardation or seizures. Neurological examination and developmental milestones were normal. None of family members had any findings suggestive of neurofibromatosis.

Figure 1: (a) and (b) Multiple CALMs with regular margins over back and thigh

Figure 3: (a) Proptosis of left eye. (b) MRI brain showing ill-defined area of altered intensity noted over left upper eyelid and extraconal compartment on superotemoral aspect of left orbit with minimal inferior displacement of left eyeball

Considering these clinical features, the differential diagnoses were NF1 and McCune–Albright syndrome.

Routine investigations were normal. On ophthalmic examination, lisch nodules were absent. No X-ray findings suggestive of fibrous dysplasia of bone were noted. Histopathological examination of large patch revealed basal hyperpigmentation with increased focal basal melanocytes which was suggestive of CALM.

Based on clinical features and investigations, a diagnosis of NF1 with giant segmental CALM was made. Genetic counseling was advised to parents. Patient was referred to pediatrician and neurologist for examination and was asked to follow up in our Outpatient department (OPD).

Multiple CALMs are observed in genetic diseases like NF1, McCune–Albright syndrome and Noonan’s syndrome.[6] CALMs are sharply defined, light-brown patches that vary in size from 0.5 to 50 cm, although the majority are 10 cm or less in size. Giant CALMs larger than 30 cm since birth are not usual.[2]

SNF is defined as CALMs or neurofibromas in a single, unilateral segment of the body.[3],[7] These lesions do not cross midline.[3],[7] There is no family history. Systemic involvement is rare. Type I segmental manifestations of NF1 represent SNF.[5] In SNF, mutation occurs late during the embryonic development that provokes localized disease.[4],[5]

Type II manifestations which occurs due to loss of heterozygosity (LOH) that occurs at an early stage of embryogenesis.[4],[5],[8] It manifests as segmental disease may be superimposed on classical generalized disease. Type II segmental manifestation of autosomal dominant dermatoses characterized by pronounced segmental lesions superimposed on the ordinary nonsegmental phenotype.[4],[5] Type II manifestations have been reported in the form of plexiform neurofibroma and giant CALM in NF1.[9],[10],[11]

LOH is the segmental loss of remaining allele which may give rise to segments of body with exaggerated presentation of autosomal dominant conditions. Patients who present with SNF with axillary freckling, CALMs or lisch nodule are explained on the basis of LOH than mosaicism. The risk of passing gene to child is 50:50.[8]

We describe a case of NF1 in child with a giant CALM. Giant CALM in NF1 can be explained on the basis of type II segmental manifestations of autosomal dominant disorders.

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